1. Field of the Invention
The invention relates to a novel process for the preparation of N-(amino-4,6-dihalopyrimidine)-formamides of the formula ##STR3##
starting from a 2,5-diamino-4,6-dihalopyrimidine of the general formula ##STR4##
2. Back of the Invention
N-(Amino-4,6-dihalopyrimidine)formamides such as N-(2-amino-4,6-dihalopyrimidin-5-yl)formamide are important intermediates for the production of antiviral nucleotide derivatives (EP-A 0 684 236).
To date, a number of processes for the preparation of N-(2-amino-4,6-dihalopyrimidin-5-yl)formamide have been disclosed. Thus EP-A 0 684 236, for example, describes a process for the preparation of N-(2-amino-4,6-dihalopyrimidin-5-yl)formamide starting from an aminomalonic ester. In this process, the aminomalonic ester is first cyclized to 2,5-diamino-4,6-dihydroxypyrimidine with guanidine in the presence of an alkoxide and then 4,6-dichloro-N'-(dimethylaminomethylene)pyrimidine-2,5-diamine is formed from this with phosphorus oxychloride in the presence of dimethylformamide. The latter is subsequently converted into the desired product using aqueous propionic acid.
The disadvantages of this process are, on the one hand, the moderate yield of desired product and, on the other hand, the fact that this process proceeds via 3 stages.
To date, a number of processes for the preparation of 2,5-diamino-4,6-dihalopyrimidines such as 2,5-diamino-4,6-dichloropyrimidine have also been disclosed. For example, WO 91/01310 describes a process for the preparation of 2,5-diamino-4,6-dichloropyrimidine starting from 2,5-diamino-4,6-dihydroxypyrimidine in the presence of phosphorus oxychloride and a quaternary ammonium halide or a weakly basic tertiary amine or its salt. In this process, the phosphorus oxychloride serves as a solvent.
This process has the disadvantage that it is not reproducible on the industrial scale and the desired final product is only obtained in low yield.